EP0952831A1 - Paroxetine compositions - Google Patents
Paroxetine compositionsInfo
- Publication number
- EP0952831A1 EP0952831A1 EP98900575A EP98900575A EP0952831A1 EP 0952831 A1 EP0952831 A1 EP 0952831A1 EP 98900575 A EP98900575 A EP 98900575A EP 98900575 A EP98900575 A EP 98900575A EP 0952831 A1 EP0952831 A1 EP 0952831A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- paroxetine hydrochloride
- spray
- dried
- process according
- disorders
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 75
- 239000000203 mixture Substances 0.000 title claims abstract description 15
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 title claims abstract description 8
- 229960002296 paroxetine Drugs 0.000 title claims abstract description 8
- 229960005183 paroxetine hydrochloride Drugs 0.000 claims abstract description 34
- 238000001694 spray drying Methods 0.000 claims abstract description 10
- 239000000243 solution Substances 0.000 claims abstract description 9
- 239000007787 solid Substances 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 238000009472 formulation Methods 0.000 abstract description 6
- 239000002245 particle Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000002271 trichotillomania Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Paroxetine hydrochloride is obtained in a free-flowing and easily soluble form (suitable for preparing solid formulations or aqueous solutions, suitable for parenteral use) by spray-drying solutions of paroxetine hydrochloride hemihydrate or other anhydrate/hydrate/solvate/amorphous forms.
Description
PAROXETINE COMPOSITIONS
The present invention relates to a process for the preparation of a pharmaceutically active compound, and to use of the so-prepared compound in therapy. In particular this invention is concerned with the preparation of a free-flowing form of paroxetine hydrochloride.
Pharmaceutical products with antidepressant and anti-Parkinson properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those disclosed is paroxetine, the (-)trans isomer of 4-(4'-fluorophenyl)-3',4'-methylenedioxy- phenoxymethyl)-piperidine. This compound is used in therapy as the hydrochloride salt to treat inter alia depression, obsessive compulsive disorder (OCD) and panic.
Paroxetine hydrochloride has been described in the literature as a crystalline hemihydrate (see EP-A-0223403 of Beecham Group) and as various crystalline anhydrate forms (see WO96/24595 of SmithKline Beecham pic). These known forms have properties that are not ideal for all pharmaceutical applications, and are prepared by multi-step procedures involving precipitation under carefully controlled conditions, filtration, drying, and homogenisation. The preferred crystallisation procedures utilise organic solvents which, when compared to water, are costly and are associated with safety and environmental problems. Furthermore, the difficulty of producing crystalline products with a uniform and regular particle size causes problems with formulation by encapsulation. Also, the flow characteristics of crystalline products limit the choice of bulk transfer and formulation technologies that can be used, while dust formation and electrostatic properties can be hazardous. In addition, the known sold forms of paroxetine hydrochloride are relatively insoluble and are slow to dissolve completely.
There remains a need for a form of paroxetine hydrochloride with improved processing and formulation characteristics.
According to a first aspect of the invention, there is provided a process for preparing a free- flowing form of paroxetine hydrochloride which comprises spray drying a solution of paroxetine hydrochloride.
The feedstock for spray drying may be prepared conveniently by, for example, dissolution of paroxetine free base in aqueous hydrochloric acid, although other solid forms of paroxetine hydrochloride may also be dissolved. For example, the feedstock may be prepared by dissolving amorphous paroxetine hydrochloride or a crystalline paroxetine hydrochloride anhydrate, hydrate or solvate in suitable solvent. The solvent used may be
pure water or a mixture of water with compatible organic solvents. Suitable compatible organic solvents include pyridinem acetic acid, acetonitrile, acetone, ethanol, propan-1-ol, butan-1-ol and tetrahydrofuran. Or alternatively a suitable organic solvent may be used on its own to form a solution with paroxetine hydrochloride. Some heating may be used to achieve and maintain complete solution, though once dissolved and in the absence of seeds of a crystalline form, aqueous solutions are stable at ambient temperature for many days. Suitable concentrations of paroxetine hydrochloride for spray-drying are in the range 1 to 30% by weight, preferably in the range 5% to 20% by weight.
Using conventional spray-drying procedures under normal conditions, often results in paroxetine hydrochloride particles that are sticky and adhere to the sides of the apparatus and to each other. However, when apparatus and operating conditions are selected to ensure that the particles are cooled sufficiently before they strike the apparatus walls, successful spray-drying may be carried out. Careful control of drop size in the spray nozzles, air flow rates and temperatures is needed to suit the apparatus used.
The paroxetine product of the above process is free-flowing, is readily wetted, and dissolves rapidly; solutions with high concentrations may be prepared without recourse to heating.
Accordingly, a second aspect of this invention is spray-dried paroxetine hydrochloride.
Spray-dried paroxetine hydrochloride of this invention has been found to be particularly suitable for applications where uniform particle size and good flow properties are advantageous. Furthermore as a result of the close control of particle size possible by spray-drying, the product may be handled conveniently and safely without the hazards associated with the dust produced when conventionally prepared paroxetine hydrochloride solids are prepared. Examples of applications where uniform particle size are advantageous include controlled release and microencapsulation (coated particle technology). Samples may be produced with particle sizes for specific applications, for example in the range 10-1000 microns.
Microencapsulation may be incorporated into the spray-drying process or may be carried out in a subsequent step. This technology is useful for taste masking, rapid or controlled release formulations, hence control of pharmacokinetics including the matching of pharmacokinetic properties for combination products.
Isolation of the solid product from the feedstock solution may be possible with just one processing stage; and so there is generally no need for blending, granulating, or drying, though an extra drying stage may be added if required. Providing aqueous feedstocks are used the costs and environmental problems normally associated with organic solvents are entirely avoided.
The spray-dried product of this invention may be formulated for therapy in the dosage forms described in EP-A-0223403 or WO96/24595. The free-flowing properties are advantageous for the preparation of solid formulations. Also the easily soluble nature of spray dried paroxetine hydrochloride makes it suitable for the preparation of solutions for parenteral use.
Therapeutic uses of the paroxetine product of this invention include treatment of: alcoholism, anxiety, depression, obsessive compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, pre-menstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the disorders".
Accordingly, the present invention also provides:
a pharmaceutical composition for treatment or prophylaxis of the disorders comprising spray-dried paroxetine hydrochloride and a pharmaceutically acceptable carrier or an aqueous solution of reconstituted spray-dried paroxetine hydrochloride;
the use of spray-dried paroxetine hydrochloride to manufacture a medicament in solid or reconstituted liquid form for the treatment or prophylaxis of the disorders; and
a method of treating the disorders which comprises administering an effective or prophylactic amount of spray-dried paroxetine hydrochloride as a solid oral composition or as a reconstituted aqueous oral or parenteral composition to a person suffering from one or more of the disorders.
The invention is illustrated by the following Example..
Example:
A 10%) aqueous solution of paroxetine hydrochloride is spray-dried under the following conditions:
Apparatus: Niro Fielder Mobile Minor
Inlet temperature setting: 185°C Actual inlet temperature: 184-185°C Outlet temperature: 94-95°C Atomiser speed: 40,000 - 50,000 rpm Pump speed (peristaltic): 32-34 rpm Air supply 4.8 - 5.2 bar DP across filters: Bag filter: start of run 57 mm of water end of run 65 mm of water
Hepa filter: start of run 7 mm of water end of run 7 mm of water
DP across the orifice plate: start of run 80+ mm of water end of run 80+ mm of water
Claims
1. A process for preparing a free-flowing form of paroxetine hydrochloride which comprises spray drying a solution of paroxetine hydrochloride.
2. A process according to claim 1, in which the feedstock for spray drying is prepared by dissolution of paroxetine free base in aqueous hydrochloric acid.
3. A process according to claim 1, in which the feedstock is prepared by dissolving amorphous paroxetine hydrochloride or a crystalline paroxetine hydrochloride anhydrate, hydrate or solvate in a suitable solvent.
4. A process according to claim 1 ,2 or 3, in which the solvent is pure water or a mixture of water with one or more compatible organic solvents.
5. A process according to claim 1 or 3 in which the solution of paroxetine hydrochloride is in a suitable organic solvent in the absence of water.
6. A process according to claim 4 or 5 in which the organic solvent is selected from pyridine, acetic acid, acetonitrile, acetone, ethanol, propan-1-ol, butan-1-ol, or tetrahydrofuran
7. A process according to any one of the preceding claims, wherein the concentration of paroxetine hydrochloride is in the range 5% to 20% by weight.
8. Spray-dried paroxetine hydrochloride.
9. A pharmaceutical composition for treatment or prophylaxis of the disorders comprising spray-dried paroxetine hydrochloride and a pharmaceutically acceptable carrier or an aqueous solution of reconstituted spray-dried paroxetine hydrochloride.
10. The use of spray-dried paroxetine hydrochloride to manufacture a medicament in solid or reconstituted liquid form for the treatment or prophylaxis of the disorders.
11. A method of treating the disorders which comprises administering an effective or prophylactic amount of spray-dried paroxetine hydrochloride as a solid oral composition or as a reconstituted aqueous oral or parenteral composition to a person suffering from one or more of the disorders.
12. A composition according to claim 9, use according to claim 10, or a method according to claim 11 , wherein the spray-dried paroxetine hydrochloride is the product of a process claimed in any one of claims 1 to 7.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9700692 | 1997-01-15 | ||
| GBGB9700692.8A GB9700692D0 (en) | 1997-01-15 | 1997-01-15 | Novel process and compound |
| GBGB9714873.8A GB9714873D0 (en) | 1997-07-15 | 1997-07-15 | Novel process and compound |
| GB9714873 | 1997-07-15 | ||
| PCT/GB1998/000081 WO1998031365A1 (en) | 1997-01-15 | 1998-01-12 | Paroxetine compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0952831A1 true EP0952831A1 (en) | 1999-11-03 |
Family
ID=26310796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP98900575A Withdrawn EP0952831A1 (en) | 1997-01-15 | 1998-01-12 | Paroxetine compositions |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US20010049442A1 (en) |
| EP (1) | EP0952831A1 (en) |
| JP (1) | JP2001508460A (en) |
| KR (1) | KR20000070151A (en) |
| CN (1) | CN1249686A (en) |
| AP (1) | AP9901604A0 (en) |
| AU (1) | AU730532B2 (en) |
| BG (1) | BG103648A (en) |
| BR (1) | BR9806754A (en) |
| CA (1) | CA2277480A1 (en) |
| EA (1) | EA002034B1 (en) |
| HU (1) | HUP0000960A3 (en) |
| ID (1) | ID23250A (en) |
| IL (1) | IL130856A (en) |
| NO (1) | NO993460L (en) |
| NZ (1) | NZ336587A (en) |
| OA (1) | OA11077A (en) |
| PL (1) | PL334568A1 (en) |
| SK (1) | SK95099A3 (en) |
| TR (1) | TR199901622T2 (en) |
| WO (1) | WO1998031365A1 (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9724544D0 (en) * | 1997-11-21 | 1998-01-21 | Smithkline Beecham Plc | Novel Formulation |
| US6168805B1 (en) * | 1998-05-07 | 2001-01-02 | Endo Pharmaceuticals, Inc. | Aqueous process for manufacturing paroxetine solid dispersions |
| GB9810181D0 (en) * | 1998-05-13 | 1998-07-08 | Smithkline Beecham Plc | Novel formulations |
| TR200100444T2 (en) * | 1998-08-07 | 2001-07-23 | Smithkline Beecham P.L.C. | Method of preparation of a non-crystalline anhydrate form of Paroxetine Hydrochloride |
| GB9824298D0 (en) * | 1998-11-05 | 1998-12-30 | Smithkline Beecham Plc | Novel process |
| CA2367402C (en) | 1999-03-12 | 2010-11-23 | Basf Aktiengesellschaft | Stable pharmaceutical dosage form for paroxetine anhydrate |
| GB9914600D0 (en) * | 1999-06-22 | 1999-08-25 | Smithkline Beecham Plc | Novel,process |
| ES2162560B1 (en) * | 1999-06-25 | 2002-07-16 | Rodriguez Concepcion Pena | USE OF FLUOXETINA, PAROXETINA AND OTHER SSRIs FOR THE MANUFACTURE OF MEDICINES IN ORDER TO INCREASE THE CAPACITY OF ABSTENTION OF SUBSTANCES OR ACTIVITIES THAT CREATE DEPENDENCE. |
| JP2003503493A (en) | 1999-07-01 | 2003-01-28 | イタルファルマコ ソシエタ ペル アチオニ | Complexes of paroxetine with cyclodextrin or cyclodextrin derivatives |
| GB9919052D0 (en) * | 1999-08-12 | 1999-10-13 | Smithkline Beecham Plc | Novel compound composition and process |
| GB9923446D0 (en) * | 1999-10-04 | 1999-12-08 | Smithkline Beecham Plc | Novel process |
| GB9923439D0 (en) * | 1999-10-04 | 1999-12-08 | Smithkline Beecham Plc | Novel process |
| US6660298B1 (en) * | 2000-07-27 | 2003-12-09 | Pentech Pharmaceuticals, Inc. | Paroxetine tablets and capsules |
| WO2002017921A2 (en) * | 2000-08-28 | 2002-03-07 | Synthon B.V. | Paroxetine compositions and processes for making the same |
| US20060039975A1 (en) * | 2004-08-20 | 2006-02-23 | Zalman Vilkov | Paroxetine formulations |
| CN104027306A (en) * | 2014-06-25 | 2014-09-10 | 万特制药(海南)有限公司 | Paroxetine oral suspension and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2297550B (en) * | 1995-02-06 | 1997-04-09 | Smithkline Beecham Plc | Paroxetine hydrochloride anhydrate substantially free of bound organic solvent |
| CA2206592A1 (en) * | 1996-05-30 | 1997-11-30 | Shu-Zhong Wang | Method of producing amorphous paroxetine hydrochloride |
-
1998
- 1998-01-12 SK SK950-99A patent/SK95099A3/en unknown
- 1998-01-12 ID IDW990687A patent/ID23250A/en unknown
- 1998-01-12 CA CA002277480A patent/CA2277480A1/en not_active Abandoned
- 1998-01-12 IL IL13085698A patent/IL130856A/en not_active IP Right Cessation
- 1998-01-12 PL PL98334568A patent/PL334568A1/en unknown
- 1998-01-12 BR BR9806754-0A patent/BR9806754A/en not_active IP Right Cessation
- 1998-01-12 KR KR1019997006377A patent/KR20000070151A/en not_active Withdrawn
- 1998-01-12 AP APAP/P/1999/001604A patent/AP9901604A0/en unknown
- 1998-01-12 NZ NZ336587A patent/NZ336587A/en unknown
- 1998-01-12 HU HU0000960A patent/HUP0000960A3/en unknown
- 1998-01-12 TR TR1999/01622T patent/TR199901622T2/en unknown
- 1998-01-12 WO PCT/GB1998/000081 patent/WO1998031365A1/en not_active Ceased
- 1998-01-12 CN CN98803170A patent/CN1249686A/en active Pending
- 1998-01-12 EP EP98900575A patent/EP0952831A1/en not_active Withdrawn
- 1998-01-12 JP JP53392198A patent/JP2001508460A/en active Pending
- 1998-01-12 AU AU55673/98A patent/AU730532B2/en not_active Ceased
- 1998-01-12 EA EA199900655A patent/EA002034B1/en not_active IP Right Cessation
-
1999
- 1999-07-14 NO NO993460A patent/NO993460L/en not_active Application Discontinuation
- 1999-07-15 OA OA9900158A patent/OA11077A/en unknown
- 1999-08-10 BG BG103648A patent/BG103648A/en unknown
-
2001
- 2001-08-03 US US09/922,072 patent/US20010049442A1/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9831365A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ID23250A (en) | 2000-03-30 |
| PL334568A1 (en) | 2000-03-13 |
| BR9806754A (en) | 2000-03-14 |
| CN1249686A (en) | 2000-04-05 |
| IL130856A (en) | 2001-09-13 |
| WO1998031365A1 (en) | 1998-07-23 |
| NO993460D0 (en) | 1999-07-14 |
| SK95099A3 (en) | 2000-01-18 |
| TR199901622T2 (en) | 1999-09-21 |
| NO993460L (en) | 1999-09-14 |
| AU5567398A (en) | 1998-08-07 |
| NZ336587A (en) | 2001-01-26 |
| CA2277480A1 (en) | 1998-07-23 |
| OA11077A (en) | 2003-03-13 |
| AU730532B2 (en) | 2001-03-08 |
| EA002034B1 (en) | 2001-12-24 |
| IL130856A0 (en) | 2001-01-28 |
| HUP0000960A3 (en) | 2001-04-28 |
| AP9901604A0 (en) | 1999-09-30 |
| KR20000070151A (en) | 2000-11-25 |
| BG103648A (en) | 2000-04-28 |
| JP2001508460A (en) | 2001-06-26 |
| HUP0000960A2 (en) | 2001-02-28 |
| EA199900655A1 (en) | 2000-02-28 |
| US20010049442A1 (en) | 2001-12-06 |
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